Anaerobes are an important but uncommon cause of bloodstream infections (BSIs). For pediatric patients, routine inclusion of an anaerobic blood culture alongside the aerobic remains controversial. We implemented automatic anaerobic blood culture alongside aerobic blood cultures in a pediatric emergency department (ED) and sought to determine changes in recovery of obligate and facultative anaerobes. This was a cohort study in a pediatric ED (August 2015 to July 2018) that began in February 2017.
KEYWORDS: anaerobic blood culture, pediatric, facultative anaerobes, blood cultures, emergency medicine
ABSTRACT
Anaerobes are an important but uncommon cause of bloodstream infections (BSIs). For pediatric patients, routine inclusion of an anaerobic blood culture alongside the aerobic remains controversial. We implemented automatic anaerobic blood culture alongside aerobic blood cultures in a pediatric emergency department (ED) and sought to determine changes in recovery of obligate and facultative anaerobes. This was a cohort study in a pediatric ED (August 2015 to July 2018) that began in February 2017. Blood culture positivity results for true pathogens and contaminants were assessed, along with a secondary outcome of time to positivity (TTP) of blood culture. A total of 14,180 blood cultures (5,202 preimplementation and 8,978 postimplementation) were collected, with 8.8% (456) and 7.1% (635) positive cultures in the pre- and postimplementation phases, respectively. Of 635 positive cultures in the postimplementation phase, aerobic blood cultures recovered 7.6% (349/4,615), whereas anaerobic blood cultures recovered 6.6% (286/4,363). In 211/421 (50.0%) paired blood cultures, an organism was recovered in both cultures. The number of cases where organisms were only recovered from an aerobic or an anaerobic bottle in the paired cultures were 126 (30.0%) and 84 (20.0%), respectively. The TTP was comparable regardless of bottle type. Recovery of true pathogens from blood cultures was approximately 7 h faster than recovery of contaminants. Although inclusion of anaerobic blood cultures only recovered 2 (0.69%) obligate anaerobes, it did allow for recovery of clinically significant pathogens that were negative in aerobic blood cultures and supports the routine collection of both bottles in pediatric patients with a concern of bloodstream infections.
INTRODUCTION
Anaerobes are an important cause of bloodstream infections (BSIs), including bacteremia, sepsis, and septic shock, and account for up to 20% of all cases of bacteremia (1). In contrast to adults, routine inclusion of an anaerobic blood culture alongside the aerobic culture for pediatric patients remains controversial (1). While the spectrum of pathogens associated with pediatric BSI is greatly dependent on patient age and immune status, the pathogens associated with BSI in children tend to be caused by aerobic and facultative anaerobes (2, 3). Since infections with obligate anaerobes are less common, some studies support limiting routine collection of anaerobic cultures in children except for those at increased risk, such as immunocompromised patients, and those who meet specific risk criteria, such as intraabdominal infections (4–6). In immunocompetent children, specific conditions predispose them to anaerobic bacteremia, such as peritonsillar abscesses caused by such organisms as Fusobacterium necrophorum and Bacteroides species, patients with dental decay undergoing dental manipulation or extraction, or other maxillofacial abscesses with baseline low-oxygen conditions. Aside from these specific disease conditions (7), others propose empirical treatment of adult and pediatric anaerobic bacteremia without any laboratory confirmation (8, 9).
In contrast, supporters of routine rather than selective anaerobic blood cultures emphasize the striking increase in incidences of obligate anaerobic BSIs and the associated consequences in patients with inappropriate anaerobic coverage (10, 11). Epidemiological evidence demonstrates that the bulk of patients who succumb to anaerobic infections are either immunocompromised (i.e., hematologic malignancy) or those who develop central line infections (7). Unfortunately, studies have also shown that treatment of these patients for presumed anaerobic BSIs, without a diagnostic anaerobic culture, results in increased mortality of up to 55% (12). Lastly, anaerobic blood cultures may also contribute to the recovery of facultative anaerobes (8, 13).
There is a paucity of current data on the significance and utility of routine anaerobic blood cultures in children. Current practice documents provide limited guidance regarding anaerobic blood cultures in children. The 2013 Infectious Disease Society of America and American Society of Microbiology practice guidelines recommend only aerobic blood cultures be collected in children (14), and the 2018 practice guidelines recommend anaerobic culture when “clinically relevant,” but with no further explanation (15). Moreover, a recent review on the diagnosis of BSIs in children addressed the common blood volume limitations and recommended restriction of anaerobic blood cultures to patients at increased risk of anaerobic bacteremia (10). Despite these recommendations, clinical practice varies significantly across medical centers, as indicated by an American Academy of Pediatrics perinatal survey that reported only 50% of providers order aerobic cultures without anaerobic cultures (16).
Historically, our institution did not offer routine anaerobic blood cultures. To determine the effect of adding routine anaerobic blood cultures in a large freestanding pediatric medical center, we implemented automatic anaerobic blood cultures alongside every aerobic blood culture ordered in the emergency department (ED). Herein, we sought to assess whether the inclusion of anaerobic blood cultures in our ED improved recovery of both obligate and facultative anaerobes and contributed to the diagnosis of BSIs.
MATERIALS AND METHODS
Ethics statement.
This was a prospective and retrospective cohort study during a planned departmental change to incorporate routine anaerobe blood cultures to all aerobe blood culture orders for a total of 36 months. This study was approved by the local institutional review board. The ED is located in a single, freestanding urban tertiary children’s hospital ED with an annual patient volume of approximately 94,000 patients a year, almost all of whom are less than 18 years of age. We included all patients who had any blood cultures drawn during the ED visit. Patients who were discharged after the specimen procurement were still included; however, we did not include any samples or results procured outside the ED, such as from outside medical facilities or other hospital units outside the ED.
Clinical samples.
Blood cultures from pediatric patients submitted for routine workup to the clinical microbiology laboratory were included in the study. Prior to implementation, anaerobic blood cultures were collected at the treating physician’s discretion. In the preimplementation phase, the ED policy defined a blood culture set as one aerobic blood culture bottle. If the patient is admitted, additional blood culture sets may be collected within a 24-h period based on the primary physician’s discretion. In the postimplementation phase, a blood culture set collected in the ED alone was defined as one aerobic and one anaerobic blood culture bottle. Each blood culture set was counted individually, and analysis by patient or blood culture episode was not conducted.
Anaerobe blood culture implementation process.
The ED started protocolized routine anaerobe culture collection (postimplementation phase) beginning 1 February 2017. In preparation, the authors used multiple email reminders, workshops, and nursing shift huddle reminders for 3 months, with department-wide reporting of compliance to this protocol and just-in-time in-services as needed on a rolling basis. We set the a priori goal of maintaining a 90% compliance with a fail threshold of 80%. In other words, if 80% of aerobic cultures were not paired with an anaerobic culture during any given month, the protocol would end. Both physician and nursing leadership received monthly metrics.
Blood culture workup.
The workup of positive blood cultures was consistent throughout the pre- and postimplementation arms. Per institution protocol, determination of sufficient blood volume to be collected for blood cultures is based on the patient’s weight. Specifically, nurses and phlebotomists are expected to collect at least 1 ml of blood for each individual bottle. For the postimplementation phase, continuous nursing education was conducted to ensure that sufficient blood volume (>1 ml each bottle) was inoculated in both bottles. Intermittent audits were initiated 5 months prior to postimplementation phase, which consisted of weighing ∼10% of all blood culture bottles received in the microbiology laboratory from all units. Specific blood volume data from the ED alone were not available. Bottles were weighed before and after inoculation of blood, and all bottles with <1 ml volume were identified. The criteria for the audit was set at <1 ml to be classified as insufficient, and further education was provided to the implicated units.
Blood was inoculated into Bactec Plus Aerobic/F or Bactec Peds Plus/F (for aerobic) and BD Bactec Lytic/10 Anaerobic/F (for anaerobic) (BD, Franklin Lakes, NJ). Upon receipt in the clinical microbiology laboratory, all Bactec blood culture bottles were incubated in the Bactec FX incubator (BD, Franklin Lakes, NJ) for up to 5 days. Once positive, blood culture bottles were aseptically inoculated into blood agar, MacConkey, and chocolate agar and incubated for 18 to 24 h at 37°C and 5% CO2. An additional brucella agar plate incubated in anaerobic conditions at 37°C was also included for positive anaerobic blood cultures. A Gram stain slide was also prepared and reported within 1 h of positivity. Blood cultures with Gram-positive organisms seen on Gram stain were tested by Verigene Gram-positive blood culture (BC-GP) panel (Luminex Corporation, Austin, TX), and blood cultures positive for Gram-negative organisms were tested by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), either directly from broth (17) or from the isolate after incubation.
Data collection.
Data were procured from the clinical microbiology reports for all submitted blood cultures, filtered for ED specimens only. These included date and time stamps of the specimen order, laboratory receipt, preliminary positivity, and final identification results. The only patient-level data available were age, and clinical indication for the blood culture(s) was not collected for this study. Medical chart abstraction was conducted in a subset of patients who had organisms recovered from anaerobic blood cultures only. Data were collected using records from 1 August 2015 through 31 July 2018; this resulted in 18 months of data prior to and after the anaerobe culture protocol implementation.
The independent variables include phase, separated into the binary pre- versus postimplementation phase of the anaerobe blood culture protocol, as well as the type of culture between aerobic and anaerobic. A 2-by-2 model was not possible because of the low number of anaerobic cultures during the preimplementation phase.
The primary outcome for this study was positive culture, defined as any growth upon final culture result. A positive culture was deemed a contaminant if only one blood culture set out of at least 2 blood cultures sets collected within a 24-h period was positive for one of the following organisms: coagulase-negative staphylococci (CoNS), viridans group streptococci (VGS), Corynebacterium species (not Corynebacterium jeikeium), Bacillus species (not Bacillus anthracis), Micrococcus species, and Cutibacterium acnes. If only one blood culture set was collected within a 24-h period (not uncommon in children), then, by definition, it cannot be considered a contaminant. Recognizing this limitation, we also made the secondary assumption that all time-to-positivity (i.e., growth detected in an automated system) results of >36 h for the common skin flora listed above were contaminants. A secondary outcome for the study included time-to-blood culture positivity of organisms recovered from aerobic and anaerobic blood cultures.
Statistical analysis.
Descriptive statistics were used to summarize the data within the 36-month time period, including a time-series graph to document implementation and compliance with the protocol. The primary analysis used was Fisher’s exact test; this included analyses of rates of positive cultures and analyses on pathogens versus contaminants. Secondary analyses for the outcome variables of time duration (e.g., time to positive culture) employed nonparametric testing because we anticipated a priori a nonnormal distribution, particularly with contaminant cultures. All analyses were done using SPSS version 24 (Armonk, NY).
RESULTS
In total, 5,202 blood cultures were collected from the ED during the preimplementation phase and 8,978 cultures during the postimplementation phase. The children included for these cultures were a mean age of 6.5 ± 6.3 years old. One culture during the preimplementation phase had a data error and was excluded. A total of 1,091 (7.7%) blood cultures were found to be positive during the 36 months (Table 1). The overall compliance rate was measured for 18 months, and, other than the first month of implementation, the rate of compliance was above the goal of 90% (Fig. 1). A hospital-wide blood volume audit revealed that the percent of sufficient blood volume did not change between the two phases (88.2 versus 87.1%), but there was a slight decrease in the median blood volume by 0.3 ml (3.4 ml versus 3.0 ml) in the postimplementation phase. The decrease was due to a significant decrease in median blood volume collected in the anaerobic bottle (2.2 ml) compared to the aerobic bottle (3.2 ml; P = 0.0397).
TABLE 1.
Comparisons of positive versus negative blood cultures
| Blood culture result | Data fora
: |
|||||||
|---|---|---|---|---|---|---|---|---|
| AER bottles (total) | ANA bottles (total) | All bottles (pre) | All bottles (post) | AER bottles (pre) | AER bottles (post) | ANA bottles (pre) | ANA bottles (post) | |
| No. positive (%) | 800 (8.2) | 291 (6.6) | 456 (8.8) | 635 (7.1) | 451 (8.7) | 349 (7.6) | 5 (19.2) | 286 (6.6) |
| No. negative | 8,991 | 4,098 | 4,746 | 8,343 | 4,725 | 4,266 | 21 | 4,077 |
| Total | 9,791 | 4,389 | 5,202 | 8,978 | 5,176 | 4,615 | 26 | 4,363 |
| P value | 0.001b | 0.0003c | 0.04d | |||||
AER, aerobic; ANA, anaerobic; pre, preimplantation phase; post, postimplantation phase.
P value for total AER versus ANA bottles.
P value for all bottles preimplantation versus postimplantation.
P value for AER bottles preimplantation versus AER bottles postimplantation.
FIG 1.
Depiction of compliance following implementation of anaerobic cultures during the postimplementation phase. The compliance rate \did not meet the goal of 90% only during the 1st month of implementation. The compliance rate never went below 80%.
When comparing positive cultures before and after implementation of routine anaerobic blood cultures, the difference in positivity rate was statistically significant (P < 0.001). Of the 5,202 blood cultures during the preimplementation phase, 5,176 (99.5%) were aerobic, and 26 were anaerobic (0.5%). Four hundred fifty-six cultures (8.8%) were positive in this phase, the majority of which were from aerobic blood cultures at 451/5,176 (8.7%) (Table 1). Only 5/26 (19.2%) were positive from anaerobic blood cultures, all of which were facultative anaerobes, and 4/5 were considered true pathogens. In contrast, inclusion of anaerobic blood cultures in the ED during the postimplementation phase yielded 4,615 (51.4%) aerobic blood cultures and 4,363 (48.6%) anaerobic blood cultures (total, 8,978). A total of 635 (7.6%) blood cultures were positive for an organism in the postimplementation group. Aerobic blood cultures recovered 349/4,615 (7.6%) organisms, and anaerobic blood cultures were positive in 286/4,363 (6.6%) (Table 1).
Pathogens versus contaminants.
Based on our definition of a contaminant, the rate of contaminants was not significantly different between the two phases (P = 0.6) (Table 2). Specifically, 95.6% (436/456) and 95.0% (603/635) positive cultures were classified as true pathogens in the preimplementation and postimplementation phases, respectively. In the postimplementation phase, the rate of true pathogens recovered from blood cultures was comparable between anaerobic and aerobic blood cultures (94.4% versus 95.4%; P = 0.6). Recognizing that a good portion of positive blood cultures growing normal skin flora are likely contaminants but are not identified by the definition set in place, comparison of the rate of probable contaminants based on time to positivity of >36 h of incubation yielded a rate of 77.9% and 78.3% true pathogens in aerobic and anaerobic blood cultures, respectively (data not shown), which is likely a more accurate representation of the percentage of contaminants. A list of all organisms recovered and interpreted as true pathogens or contaminants in both phases is provided in Table S1 in the supplemental material.
TABLE 2.
Comparisons of rates of contaminants in aerobic and anaerobic blood culture bottles
| Blood culture result | Data for: |
|||||
|---|---|---|---|---|---|---|
| AER bottles (total)a | ANA bottles (total) | All bottles (pre) | All bottles (post) | AER bottles (post) | ANA bottles (post) | |
| No. of pathogens (%) | 770 (95.7) | 270 (94.4) | 436 (95.6) | 603 (95.0) | 333 (95.4) | 270 (94.4) |
| No. of contaminants (%) | 35 (4.3) | 16 (5.6) | 20 (4.4) | 32 (5.0) | 16 (4.6) | 16 (5.6) |
| P value | 0.4b | 0.6c | 0.6d | |||
AER, aerobic; ANA, anaerobic; pre, preimplementation phase; post, postimplementation phase.
P value for total AER versus ANA bottles.
P value for all bottles preimplantation versus postimplantation.
P value for AER bottles postimplantation versus ANA bottles postimplantation.
Organisms recovered in the postimplementation phase.
A total of 4,449 sets (aerobic and anaerobic) of blood cultures were collected in the postimplementation period, of which 3,823 (89.9%) sets were negative after 5 days of incubation. There were 421 matched blood culture sets with organisms recovered from at least one bottle. In 211 (4.7%) blood culture sets, an organism was subcultured from both aerobic and anaerobic blood culture bottles, including 64/87 (73.6%) Enterobacterales recovered (Table 3). An organism was recovered from aerobic blood cultures only in 126 (2.8%) cases and from an anaerobic blood culture bottle only in 84 (1.9%) cases.
TABLE 3.
Positivity distribution between aerobic and anaerobic blood cultures
| Organism | AER and ANA bottles obtained (no./total no. [%]) with a culture result of:a
|
||
|---|---|---|---|
| Both positive | AER positive only | ANA positive only | |
| Achromobacter species | 0/1 | 1/1 | 0/1 |
| Acinetobacter species | 0/5 | 5/5 | 0/5 |
| Actinomyces species | 0/2 | 1/2 | 1/2 |
| Aeromonas species | 0/1 | 1/1 | 0/1 |
| Bacillus species | 2/6 | 3/6 | 1/6 |
| Brevibacterium species | 0/4 | 4/4 | 0/4 |
| Campylobacter jejuni | 0/1 | 1/1 | 0/1 |
| Candida species | 3/4 | 1/4 | 0/4 |
| Capnocytophaga species | 0/1 | 0/1 | 1/1 |
| Citrobacter species | 2/3 | 1/3 | 0/3 |
| Coagulase-negative Staphylococcus | 64/136 | 37/136 | 35/136 |
| Corynebacterium species | 0/10 | 9/10 | 1/10 |
| Cutibacterium acnes | 0/10 | 1/10 | 9/10 |
| Enterobacter species | 14/18 | 3/18 | 1/18 |
| Enterococcus faecalis | 1/4 | 2/4 | 1/4 |
| Enterococcus faecium | 1/1 | 0/1 | 0/1 |
| Escherichia coli | 20/35 | 5/35 | 10/35 |
| Fusobacterium species | 0/1 | 0/1 | 1/1 |
| Globicatella species | 1/1 | 0/1 | 0/1 |
| Granulicatella adiacens | 0/1 | 0/1 | 1/1 |
| Gemella haemolysans | 0/4 | 0/4 | 4/4 |
| Haemophilus influenzae | 0/3 | 3/3 | 0/3 |
| Klebsiella species | 18/21 | 2/21 | 1/21 |
| Lactobacillus species | 1/2 | 0/2 | 1/2 |
| Leclercia adecarboxylata | 1/1 | 0/1 | 0/1 |
| Microbacterium species | 0/1 | 1/1 | 0/1 |
| Micrococcus species | 0/9 | 9/9 | 0/9 |
| Mold | 0/2 | 2/2 | 0/2 |
| Moraxella species | 0/5 | 5/5 | 0/5 |
| Pantoea species | 1/1 | 0/1 | 0/1 |
| Parvimonas micra | 0/1 | 0/1 | 1/1 |
| Proteus mirabilis | 1/1 | 0/1 | 0/1 |
| Pseudomonas species | 0/3 | 3/3 | 0/3 |
| Raoultella ornithinolytica | 1/1 | 0/1 | 0/1 |
| Rhizobium radiobacter | 0/4 | 4/4 | 0/4 |
| Rothia species | 0/1 | 1/1 | 0/1 |
| Salmonella species | 5/5 | 0/5 | 0/5 |
| Serratia marcescens | 3/3 | 0/3 | 0/3 |
| Staphylococcus aureus | 38/47 | 4/47 | 5/47 |
| Stenotrophomonas maltophilia | 0/3 | 3/3 | 0/3 |
| Streptococcus agalactiae | 6/10 | 2/10 | 2/10 |
| Streptococcus anginosus group | 1/3 | 1/3 | 1/3 |
| Viridans group Streptococcus | 16/31 | 10/31 | 5/31 |
| Streptococcus pneumoniae | 8/10 | 0/10 | 2/10 |
| Streptococcus pyogenes | 3/4 | 1/4 | 0/4 |
| Total | 211/421 (50.0%) | 126/421 (30.0%) | 84/421 (20.0%) |
AER, aerobic; ANA, anaerobic.
Of the 126 aerobic-only positive blood cultures, 61 (48.5%) grew common skin flora compared to 51/84 (60.7%) common skin flora recovered from anaerobic blood cultures only, including 9 (10.7%) C. acnes. Compared to the total number of organisms recovered from the 421 matched sets, 30.0% of all positives were recovered solely from anaerobic blood cultures. Specifically, anaerobic blood cultures only represented 28.6% (10/35) of all Escherichia coli recovered and 17.9% (10/56) of 5 clinically relevant Gram-positive cocci (Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus anginosus group) recovered. There were also two obligate anaerobes (Fusobacterium nucleatum and Parvimonas micra) recovered in the postimplementation phase (Table 3).
Time to positivity between blood culture bottles.
Data on time to positivity were available on a total of 211 blood cultures sets with identical culture growth. The median time to positivity in anaerobic cultures did not differ from aerobic cultures (12.0 versus 13.0 h; P = 0.4). Identical median times to detection of true pathogens were also calculated. Interestingly, true pathogens were detected approximately 7 h earlier (P = 0.01) than contaminants. No difference in time to positivity between aerobic and anaerobic cultures was observed for contaminants (Table 4).
TABLE 4.
Time to blood culture positivity rates in the postimplementation phase
| Blood culture positivity (no. of positive results) | Median (IQRa
) time to blood culture positivity (h) for: |
P value | |
|---|---|---|---|
| Aerobic bottles | Anaerobic bottles | ||
| All cultures (211) | 13.0 (9.0–19.0) | 12.0 (9.0–19.0) | 0.4 |
| Pathogens (203) | 13.0 (9.0–18.3) | 12.0 (9.0–16.6) | 0.9 |
| Contaminants (8) | 19.8 (18.8–22.8) | 19.0 (19.0–21.9) | 0.9 |
IQR, interquartile range.
Focusing on just the organisms considered true pathogens based on the study definition and omitting the polymicrobial blood cultures, there were 189 matched positive blood culture sets. The time to detection of both Gram-positive and Gram-negative pathogens was comparable regardless of the bottle type. Interestingly, the median time to detection of Gram-negative pathogens in both bottle types was 5 h (P <0.001) faster than Gram-positive pathogens (Table 5). Further analysis omitting common skin flora that meet the definition of probable contaminants at the time to positivity of >36 h yielded comparable results (data not shown).
TABLE 5.
Time to blood culture positivity rates in postimplementation phase among pathogens only
| Blood culture positivity (no. of positive results)a | Median (IQRb
) time to positivity (h) for: |
P value | |
|---|---|---|---|
| Aerobic bottles | Anaerobic bottles | ||
| Gram-positive organisms (130) | 14.0 (11.0–21.0) | 14.0 (11.0–20.5) | 0.6 |
| Gram-negative organisms (59) | 9.0 (6.4–12.0) | 9.0 (6.0–11.0) | 0.6 |
The total number of blood culture-positive results was 189.
IQR, interquartile range.
Clinical significance of anaerobic detection.
Of the 84 anaerobic-only positive blood cultures, there were 80 unique patients; 3/80 (3.8%) were admitted to the intensive care unit (ICU), and 45/80 (56.3%) had coexisting conditions, including 10 (12.5%) oncology patients. There were no deaths reported related to the BSI episodes. Approximately 51% of patients were febrile, including all 10 patients with E. coli BSIs, 5 of which were actually diagnosed with urosepsis. Additionally, two patients with S. pneumoniae and S. agalactiae BSIs were concurrently diagnosed with meningitis. Recovery of organisms solely from anaerobic blood cultures had a positive effect on antimicrobial therapy. All 12 patients with Enterobacterales detected and 4/5 patients positive with S. aureus were placed on appropriate antimicrobials upon reporting of anaerobic blood culture results. In contrast, only 11 of the 49 patients who grew normal skin flora were placed on antimicrobial therapy, although it was unclear whether it was to treat the BSI. Inclusion of anaerobic blood cultures also allowed for the diagnosis and appropriate management of a patient with Gemella haemolysans endocarditis, as the organism only grew out of the anaerobic bottle in all four blood culture sets.
Obligate anaerobes grew from anaerobic blood cultures of two patients. The first patient positive for F. nucleatum presented with fever and upper respiratory symptoms with a history of truncus arteriosis repair. The patient was discharged 24 h after admission and was not placed on antibiotics. The second patient who grew P. micra presented with worsening forehead swelling and upper respiratory symptoms. Computed tomography (CT) finding was notable for sinusitis, and the patient was given a 14-day course of amoxicillin-clavulanic acid. It was not indicated whether the provider was treating for the P. micra.
DISCUSSION
Anaerobic bacteremia remains a rare pediatric entity, and current infectious disease guidelines suggest routinely collecting only aerobic blood cultures in children and restricting anaerobic blood cultures based on patient-specific risk factors (15). Implementation of a blood culture set in the ED that includes the collection of both aerobic and anaerobic blood cultures was initiated on 1 February 2017, thus affording us the ability to study the effects of routinely collecting both cultures. Our positivity rate of 7.1% (635/8,978) in the postimplementation phase was slightly lower than the preimplementation rate (8.8%) as well as past studies that report positivity rates between 10.2 and 11.1% (18, 19). This slight change may be attributed to a number of variables, including unnecessary blood culture collection and blood volume.
It is well accepted that the volume of blood collected is the single most important factor in the recovery of blood pathogens. Low-level bacteremia in children is more common than previously thought, occurring in 38% to 68% of all pediatric patients with a positive blood culture (20, 21), and less than 1 ml of blood volume was found to be inadequate for the detection of blood pathogens (22). Although the blood volumes collected in the aerobic blood culture bottles were comparable in both phases, a significant difference in median blood volume was calculated between postimplementation aerobic blood cultures and anaerobic blood cultures, which likely contributed to the lower positivity rate in the latter. Likewise, the median blood volume of anaerobic blood cultures across the two phases was also decreased by >1 ml and may have contributed to the dramatic decrease in the percent positive. However, concrete conclusions are difficult, being that there were only 26 anaerobic blood cultures collected in the preimplementation phase.
Our study reports a very low percentage of pathogenic obligate anaerobes among all of our positive anaerobic cultures in our patient population at 0.64% (2/311). The prevalence of an anaerobic-only pathogen among all anaerobic cultures is likewise low at 0.046% (2/4,363). This low number supports previous findings that anaerobic bacteremia is extremely rare in children (2, 18, 23). Specifically, in a study from Spain on immunocompromised children under 18 years, only 3/90 bacterial organisms recovered were obligate anaerobes, and all were considered contaminants (19). Moreover, a 2004 study in a pediatric ED reported recovery of 595 bacterial organisms out of 2,675 paired blood cultures (11.1%; 595/5,350) over a 24-month period (18). In immunocompetent patients, almost all significant organisms were recovered from aerobic blood cultures. In contrast, the authors reported a low positivity rate of anaerobic cultures at 11.2% (31/278) and only in children with underlying medical conditions. In addition, no obligate anaerobes were recovered during the study period. These findings correlate with older studies that supported the inclusion of anaerobic blood cultures only in children at increased risk, such as immunocompromised patients and those with intraabdominal infections (4–6).
Despite the low recovery rate of obligate anaerobes, our study still supports the inclusion of anaerobic blood cultures in children based on the increased recovery of facultative anaerobes (n = 84) solely from anaerobic blood cultures, of which 39% were inarguably true pathogens, including Enterobacterales, S. aureus, S. pneumoniae, and S. agalactiae. Our findings are comparable to other studies, including a recent study reporting an increase in recovery of S. pneumoniae (24%), S. aureus (25%), and E. coli (24%) from anaerobic culture bottles alone (13). Similarly, a Japanese study of 24,356 paired blood cultures identified increased recovery of facultative anaerobes from anaerobic blood cultures, including 29% of E. coli and 15% of staphylococci (24).
Anaerobic cultures were not substantially detectable more quickly than aerobic cultures in our cohort. This is in line with findings from a past study of 9,390 paired blood cultures from children where the detection of organisms from anaerobic bottles was faster in only 2.7% of cases (3). Further, a recent pediatric study reported a faster time to detection by an average of 5.2 h in aerobic bottles (25). When looking at groups of organisms, a recent 1-year retrospective joint pediatric and adult study reported a faster recovery rate of Enterobacterales from anaerobic blood culture bottles, but time to detection of Gram-positive organisms such as S. aureus was faster in aerobic blood culture bottles (26). Synthesizing the studies does not provide uniform evidence that anaerobic cultures turn positive more quickly than aerobic cultures; furthermore, the differences seen in the literature may not lead to clinical benefits in the real-world environment. The strength of anaerobic cultures in pediatric patients with suspected BSI lies not in earlier detection but detection of organisms that are missed completely by the aerobic culture.
There are several study limitations to our study. It was conducted in a single-center, urban academic children’s hospital with a large population of immunocompromised patients, thus limiting generalizability. Unfortunately, we did not access clinical data for all patients; all blood cultures were treated independently, so no per-patient analyses or per-bloodstream infection episodes were performed. In addition, not all blood culture bottles submitted for this study were weighed, and we cannot rule out any disparity between collected blood volume in one bottle versus the other bottle. Although we were able to provide some aerobic and anaerobic median volume data, they only represented approximately 10% of all blood cultures submitted to the microbiology laboratory, and we were unable to differentiate the blood cultures submitted through the ED from other wards. Nonetheless, being that the increase in anaerobic blood cultures in the postimplementation phase was from the ED, we can deduce that the calculated anaerobic blood volume is likely representative of ED practice. We also addressed this potential limitation with repeated education throughout the study period to ensure that a standardized blood volume was inoculated into both bottles.
Overall, our study supports the ability to implement the routine collection of both sets of blood cultures without increasing contamination rates. Clinically significant bacterial pathogens were identified from anaerobic blood culture samples, but not necessarily earlier than aerobic cultures. Nonetheless, we do recognize that appropriate diagnostic stewardship measures remain important to avoid blood cultures, both aerobic and anaerobic, when not clinically warranted.
Supplementary Material
ACKNOWLEDGMENTS
We thank the nurses in the emergency department for participating in the study and ensuring high level of compliance rates. We thank the microbiology laboratory for their diligence in receiving, processing, and working up the increase number of anaerobic blood cultures.
This study was supported by a grant from Southern California Clinical and Translational Science Institute (SC CTSI) Pilot Funding Program (grant number 5351761301) awarded to J.D.B., T.P.C., A.F., and N.L. All authors have no conflicts of interest to report.
Footnotes
Supplemental material is available online only.
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